The overall purpose of this proposal is to develop more effective ocular antifungal therapy through an increased understanding of the efficacy and pharmacokinetics of antifugal agents as they apply to the eye. We plan to continue our therapeutic studies of topical antifungal agents using our quantitative models of Candida keratitis in the rabbit eye. We will investigate the susceptibility of different growth phases of the inoculum to antifungal agents and will develop dose response data for various drugs. The predictive value of in vitro susceptibility tests will be evaluated in this model for a large series of strains and we will investigate the phenomenon of potentiation and antogonism when combinations of antifungal agents are used in vivo. The relationship of the adverse effect of steroid to the efficacy of antifungal agents will be explored with a number of isolates. We plan to continue our studies of drug levels in the eye following topical and periocular administration in order to define the kinetics of uptake and clearance. Newer drugs, particularly liposomally bound antifungal agents will be evaluated in this model.